Expression signatures of vascular complication-associated proteins in type 2 diabetes: a multiomics analysis from the FIELD study

Aims: The aim of the study is to integrate targeted transcriptomic analyses of previously identified biomarker proteins (proteomic findings) to better understand vascular complications (Cx) in Type 2 diabetes (T2D). Methods: Total RNA was extracted from baseline citrate plasma samples of 543 individuals with T2D from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Among these, 224 participants had microvascular Cx, 142 had macrovascular Cx (51 had both types of Cx) and 228 had no Cx (control group). mRNA expression was quantified using the OpenArray platform and group differences were analysed using ΔΔct values. Neutrophil elastase (NE) protein levels were measured in baseline plasma by ELISA. Results: Eleven genes were retained for focused analysis. For microCx, the largest gene expression differences were observed for clusterin (~2-fold upregulation) and integrin alpha-IIb (~50% downregulation), compared with the control group. For macroCx, clusterin exhibited the strongest upregulation (~2.5-fold), whereas apolipoprotein F showed the greatest downregulation (~20%). Comparative analysis of proteomic and transcriptomic data across study groups revealed that only 32% of gene expression differences were mirrored at the protein level. NE levels were highest in the microCx group and were significantly elevated versus control only in that group; NE levels also correlated inversely with circulating actin protein expression (R² = 0.92). Conclusion: Combining proteomic and targeted plasma transcriptomic data provides exploratory insights into biological processes associated with vascular complications in T2D and highlights NE as a candidate component of a proteolytic pathway for further investigation.